Search

Despite conventionally applied postoperative radiotherapy (PORT) in pathological N2 (pN2) stage non-small cell lung cancer (NSCLC) considering high locoregional recurrence, its survival benefit has been a continuous topic of debate. Although several randomized clinical trials have been conducted, many of them have been withdrawn or analyzed without statistical significance due to slow accrual, making it difficult to determine the efficacy of PORT. Recently, the results of large-scale randomized clinical trials have been published, which showed some improvement in disease-free survival with PORT, but finally had no impact on overall survival. Based on these results, it was expected that the debate over PORT in pN2 patients with NSCLC would come to an end. However, since pN2 patients have different clinicopathologic features, it has become more important to carefully select the patient population who will benefit from PORT. In addition, given the development of systemic treatments such as molecular-targeted therapy and immunotherapy, it is crucial to evaluate whether there is any benefit to PORT in the midst of these recent changes. Therefore, determining the optimal treatment approach for NSCLC pN2 patients remains a complex issue that requires further research and evaluation. [ABSTRACT FROM AUTHOR]

Purpose Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)-overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genomewide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen. Materials and Methods Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription-quantitative polymerase chain reaction. Results We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1, and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment. Conclusion The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers. [ABSTRACT FROM AUTHOR]

Purpose In the present study, we aimed to establish a liquid biopsy-based monitoring method using peripheral blood cell-free DNA (cfDNA) for patients with cervical cancer who underwent radical radiotherapy (RT). Materials and Methods Twenty-five patients with cervical cancer were prospectively recruited and treated with external beam RT and brachytherapy. In all patients, except one, chemotherapy was administered concurrently during RT. Whole peripheral blood samples were obtained at least twice from each patient. We performed next-generation sequencing (NGS) for the target-captured libraries (67 oncogenes and human papillomavirus [HPV] type 16/18) using 64 plasma cfDNA samples from the 25 participants. The ratio of HPV cfDNA and the variant allele frequency (VAF) in cfDNA was calculated, and their dynamic changes were monitored. The median follow-up duration was 25.4 months. Results In total, we identified 21,866 cfDNA variants. ARID1A and frameshift variants occupied the largest portion of altered genes and HIGH-grade variant types, respectively. In most cases, tumor shrinkage was followed by a decrease in the HPV ratio; however, an increase in HPV ratio indicated distant metastasis, despite the reduced tumor size. The initial HPV ratio reflecting the tumor burden was likely associated with treatment outcomes (p=0.16). We did not determine a role for serial changes in the VAF in cfDNA. Conclusion Our findings suggest that the HPV cfDNA ratio, calculated after targeted NGS, may be valuable for monitoring and predicting treatment responses. Accordingly, further validation of these findings is warranted. [ABSTRACT FROM AUTHOR]

Purpose We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. Materials and Methods We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). Results Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years. [ABSTRACT FROM AUTHOR]

Purpose We first analyzed the prognostic power of albumin-to-alkaline phosphatase ratio (AAPR) before radical radiotherapy (RT) in non-metastatic nasopharyngeal carcinoma (NPC) patients. Materials and Methods The records of 170 patients with biopsy-proven, non-metastatic NPC treated by radical RT between 1998 and 2016 at our institution were retrospectively reviewed. Median follow-up duration was 50.6 months. All patients received intensity-modulated RT and cisplatin based chemotherapy before, during, or after RT. The major treatment of patients was based on concurrent chemoradiotherapy (92.4%). The AAPR was calculated by the last value of both albumin and alkaline phosphatase within 1 month immediately preceding RT. The optimal cut-off level of AAPR was determined by using Cutoff Finder, a web-based system. Propensity score matching (PSM) analysis was performed. Results The optimal cut-off level of AAPR was 0.4876. After PSM analysis of whole cohort, an AAPR was not related to survival outcomes. In PSM analysis for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC), an AAPR ≥ 0.4876 was related to better overall survival (OS), progression-free survival (PFS), and locoregional relapse–free survival (LRRFS) (OS: hazard ratio [HR], 0.341; 95% confidence interval [CI], 0.144 to 0.805; p=0.014; PFS: HR, 0.416; 95% CI, 0.189 to 0.914; p=0.029; and LRRFS: HR, 0.243; 95% CI, 0.077 to 0.769; p=0.016, respectively). Conclusion The AAPR, inexpensive and readily derived from a routine blood test, could be an independent prognostic factor for patients with LA-NPC. And it might help physicians determine treatment plans by identifying the patient's current status. Future prospective clinical trials to validate its prognostic value are needed. [ABSTRACT FROM AUTHOR]

Purpose: To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of ß-catenin/smooth muscle actin (SMA) and PFS. Materials and Methods: Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of ß-catenin and SMA were available for 11 and 12 patients, respectively. Results: The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was no related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear ß-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700). Conclusion: PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear ß-catenin staining intensity of IHC might correlate with local recurrence. [ABSTRACT FROM AUTHOR]

Pleuropulmonary blastoma (PPB) is a rare intrathoracic neoplasm in children. Although surgery with or without chemotherapy mainly conducted, the response of radiotherapy (RT) has not been evaluated yet. For unresectable tumor, RT might be considered as one option to decrease tumor extent to relieve obstructing symptoms or to facilitate successive treatment. We report one child in whom PPB with DICER1 mutation recurred after surgery and lead to respiratory distress. She emergently received palliative RT with a relatively low dose (20 Gy), and symptoms sufficiently relieved. Even she showed an 84.3% reduction in diameter and maintained the remission status for 1 year. These might reflect possible radiosensitivity of PPB, and further investigations of RT might be necessary for unresectable PPB. [ABSTRACT FROM AUTHOR]

In this study, the authors analyse the effects of the design parameters of a high-power bipolar short-pulsed array antenna on a beamwidth and a sidelobe of a transient radiation pattern. The analysed results can provide guidelines for synthesising a desired transient radiation performance of high-power bipolar short pulsed-array antennas. The analysis is performed using a formulation that consists of an element pattern and an array factor of a transient radiation pattern. To verify the validation of the studies, the analysed results of various array configurations (1 × 3, 1 × 4, 3 × 1, 4 × 1 and 2 × 2 arrays) are compared to the full-wave simulated and measured results. [ABSTRACT FROM AUTHOR]

Background: To develop a targeting therapy for hormone-independent prostate cancer, we constructed and characterized conditionally replicating oncolytic adenovirus (Ad) equipped with mRFP (monomeric red fluorescence protein)/ttk (modified herpes simplex virus thymidine kinase). This construct was then further modified to express both mRFP/ttk and a soluble form of cytokine FLT3L (fms-related tyrosine kinase 3 ligand) simultaneously. Methods: To construct the recombinant oncolytic adenovirus, E1a and E4 genes, which are necessary for adenovirus replication, were controlled by the prostate-specific enhancer sequence (PSES) targeting prostate cancer cells expressing prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA). Simultaneously, it expressed the mRFP/ttk fusion protein in order to be able to elicit the cytotoxic effect. Results: The Ad5/35PSES.mRFP/ttk chimeric recombinant adenovirus was generated successfully. When replication of Ad5/35PSES.mRFP/ttk was evaluated in prostate cancer cell lines under fluorescence microscopy, red fluorescence intensity increased more in LNCaP cells, suggesting that the mRFP/ttk fusion protein was folded functionally. In addition, the replication assay including wild-type adenovirus as a positive control showed that PSES-positive cells (LNCaP and CWR22rv) permitted virus replication but not PSES-negative cells (DU145 and PC3). Next, we evaluated the killing activity of this recombinant adenovirus. The Ad5/35PSES.mRFP/ttk killed LNCaP and CWR22rv more effectively. Unlike PSES-positive cells, DU145 and PC3 were resistant to killing by this recombinant adenovirus. Finally, in order to potentiate therapeutic efficacy, we developed a recombinant adenovirus expressing multiexogenous genes, mRFP/ttk and sFLT3L. Conclusion: In the present study, a replication-competent adenovirus was successfully designed to replicate conditionally in PSA-positive and PSMA-positive prostate cancer cells. This recombinant adenovirus is equipped with the fusion protein of suicidal and red-fluorescence fusion protein together with sFLT3L. This construct would be expected to have potent antitumor effects and deserves more extensive investigation [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of double-J stenting as an initial procedure to manage ureteral injuries detected late after gynecological surgery. Eight patients whom the insertion of double-J stent was done primarily were evaluated. Medical records were investigated retrospectively. Ureteral injuries were unilateral in seven and in one patient was bilateral (nine ureters in total). In two patients that double-J stentings were failed underwent open surgery. In six patients (seven ureters), double-J stentings were successful either by cystoscopy or ureteroscopy and four ureters were recovered without sequelae. However, in three ureters, stenosis was remained and managed by ureteral dilation with placement of double-J stent. But, one was lost at follow-up schedule. Ureteral double-J stenting, as first-line treatment, could avoid invasive urological surgery in damaged ureter detected after gynecological surgery. More cases are needed for accurate conclusions. [ABSTRACT FROM AUTHOR]

The sintering behavior and high frequency electro-magnetic properties of Ba3Co2Fe24O41 ceramics were investigated for the small antenna application. All samples of the Ba3Co2Fe24O41 ceramics were prepared by the solid-state reaction method and sintered at 1150°C 1400°C. From the XRD patterns of calcined Ba3Co2Fe24O41 powders, the most suitable condition for calcining was 600°C–1000°C. Ba3Co2Fe24O41 phase was observed in sintered Ba3Co2Fe24O41 ceramics as main phase. Bulk densities increased with sintering temperature and decreased at 1400°C. Permittivity and permeability of the Ba3Co2Fe24O41 ceramics increased or decreased with sintering temperature, respectively. On the other hand, loss tangent of permittivity and of permeability showed contrary tendency with permittivity and permeability. The permittivity and loss tangent of permittivity of Ba3Co2Fe24O41 ceramics sintered at 1300°C were 19.896 and 0.171 at 210 MHz. and the measured value of permeability and loss tangent of permeability were 14.218 and 0.204, respectively. [ABSTRACT FROM AUTHOR]

A single-layer reflectarray with a combination of element types is proposed. Three element types--square patch, square ring and ring-loaded patch (RLP)--are used together to design the reflectarray by compensating for the drawbacks of one type by the others. The gain of the proposed reflectarray is 29.1 dBi, which is 1.9 dB higher than that of the reference reflectarray that was designed with only the RLP. [ABSTRACT FROM AUTHOR]